Primary structure of protein:
Each protein has a unique sequence of amino acids which is determined by the genes contained in
DNA.
The primary structure of a protein is largely responsible for its function.
A vast majority of genetic diseases are due to abnormalities in the amino acid sequences of
proteins i.e. changes associated with primary structure of protein.
The amino acid composition of a protein determines its physical and chemical properties.
Secondary structure of protein:
The conformation of polypeptide chain by twisting or folding is referred to as secondary structure.
The amino acids are located close to each other in their sequence. Two types of secondary
structures, α-helix and β-sheet, are mainly identified.
Indian scientist Ramachandran made a significant contribution in understanding the spatial
arrangement of polypeptide chains.
α-Helix
α-Helix is the most common spiral structure of protein.
lt has a rigid arrangement of polypeptide chain.
α-Helical structure was proposed by Pauling and Corey (1951) which is regarded as one of the
milestones in the biochemistry research.
The α-helix is a tightly packed coiled structure with amino acid side chains extending outward from
the central axis.
The α-helix is stabilized by extensive hydrogen bonding. lt is formed between H atom attached to
peptide N, and O atom attached to peptide C. The hydrogen bonds are individually weak but
collectively, they are strong enough to stabilize the helix.
All the peptide bonds, except the first and last in a polypeptide chain, participate in hydrogen
bonding.
Each turn of α-helix contains 3.5 amino acids and travels a distance of 0.54 nm. The spacing of each
amino acid is 0.15 nm.
a-Helix is a stable conformation formed spontaneously with the lowest energy.
The right handed α-helix is more stable than left handed helix (a right handed helix turns in the
direction that the fingers of right hand curl when its thumb points in the direction the helix rises).
Certain amino acids (particularly proline) disrupt the α-helix. Large number of acidic (Asp, Glu) or
basic (Lys, Arg, His) amino acids also interfere with α-helix structure.
β-Pleated sheet:
This is the second type of structure proposed by Pauling and Corey.
β-Pleated sheets (or simply p-sheets) are composed of two or more segments of fully extended
peptide chains
ln the β-sheets, the hydrogen bonds are formed between the neighbouring segments of
polypeptide chain(s).
The polypeptide chains in the β-sheets may be arranged either in parallel (the same direction) or
anti-parallel (opposite direction).
β-Pleated sheet may be formed either by separate polypeptide chains (H-bonds are interchain) or a
single polypeptide chain folding back on to itself (H-bonds are intrachain)
Many proteins contain β-pleated sheets. As such, the α-helix and β-sheet are commonly found in
the same protein structure.
In the globular proteins, β-sheets form the core structure.
Other types of secondary structures: Besides the α-and β-structures described above, the β-bends and
nonrepetitive (less organised structures) secondary structures are also found in proteins.
Tertiary structure:
The three-dimensional arrangement of protein structure is referred to as tertiary structure.
lt is a compact structure with hydrophobic side chains held interior while the hydrophilic groups
are on the surface of the protein molecule.
This type of arrangement ensures stability of the molecule.
Bonds of tertiary structure: Besides the hydrogen bonds, disulfide bonds (-S-S), ionic interactions
(electrostatic bonds) and hydrophobic interactions also contribute to the tertiary structure of
proteins.
Domains: The term domain is used to represent the basic units of protein structure (tertiary) and
function. A polypeptide with 200 amino acids normally consists of two or more domains.
Tertiary structure:
A great majority of the proteins are composed of single polypeptide chains.
Some of the proteins, however, consist of two or more polypeptides which may be identical or
unrelated.
Such proteins are termed as oligomers and possess quaternary structure.
The individual polypeptide chains are known as monomers, protomers or subunits.
A dimer consist of two polypeptides while a tetramer has four.
Bonds in quaternary structure: The monomeric subunits are held together by non-covalent bonds
namely hydrogen bonds, hydrophobic interactions and ionic bonds.
Importance of oligomeric proteins: These proteins play a significant role in the regulation of
metabolism and cellular function. Examples of oligomeric proteins: Hemoglobin, aspartate
transcarbomylase, lactate dehydrogenase
